DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20190486

Esomeprazole and pantoprazole enhance the antiproliferative effects of cisplatin on the human neuroblastoma SH-SY5Y cell line

Mustafa Karademir, Merve Ergül

Abstract


Background: Proton pump inhibitors (PPIs) largely used a drug to treat gastroesophageal disease such as gastric ulcers. Moreover, in recent years, several studies suggest that PPIs have an important anti-cancer effect in monotherapy and or combination with chemotherapy. The aim of this study was to investigate whether esomeprazole and pantoprazole exhibit anti-cancer effect alone or could enhance chemosensitivity on the human neuroblastoma cell line SH-SY5Y to cisplatin.

Methods: The human neuroblastoma SH-SY5Y cells were cultured and treated with different concentrations of esomeprazole, pantoprazole, and cisplatin alone. Also, these cells exposed to cisplatin+ esomeprazole and cisplatin + pantoprazole combinations, respectively and incubated 24 h. The antiproliferative activities of the (PPIs) alone or in a combination of cisplatin was evaluated using the XTT colorimetric assay.

Results: According to experimental data, neither PPIs showed no cytotoxicity on the human neuroblastoma cell line SH-SY5Y at all concentrations. However, when combined with cisplatin separately, they were found to have significant antiproliferative effects on the human neuroblastoma SH-SY5Y cell lines when compared to cell lines treated with cisplatin alone (p<0.05).

Conclusions: Taken together, the inhibition of V-ATPase via esomeprazole and pantoprazole might enhance the chemosensitivity of cisplatin on the human neuroblastoma cell line SH-SY5Y. However, further studies are needed to be able to utilize PPIs in human neuroblastoma cells.


Keywords


Cisplatin, Esomeprazole, Human neuroblastoma SH-SY5Y cell line, Pantoprazole, V-ATPase

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References


Simpson JK, Gaze MN. Current management of neuroblastoma. The oncologist. 1998 Aug 1;3(4):253-62.

Chu CM, Rasalkar DD, Hu YJ, Cheng FWT, Li CK, Chu WCW. Clinical presentations and imaging findings of neuroblastoma beyond abdominal mass and a review of imaging algorithm. Br J Radiol. 2011;84(997):81-91.

Donzelli E, Carfì M, Miloso M, Strada A, Galbiati S, Bayssas M, et al. Neurotoxicity of platinum compounds: Comparison of the effects of cisplatin and oxaliplatin on the human neuroblastoma cell line SH-SY5Y. J Neurooncol. 2004;67(1-2):65-73.

Wang BY, Zhang J, Wang JL, Sun S, Wang ZH, Wang LP, et al. Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer. J Exp Clin Cancer Res. J Exp Clin Cancer Res. 2015;34(1):1-12.

Yilmaztepe Oral A, Oral HB, Sarimahmut M, Cevatemre B, Özkaya G, Korkmaz Ş, et al. Combination of esomeprazole with chemotherapeutics results in more pronounced cytotoxic effect via apoptosis on A549 nonsmall-cell lung cancer cell line. Turkish J Biol. 2017;41(1):231-41.

Iessi E, Logozzi M, Mizzoni D, Di Raimo R, Supuran CT, Fais S. Rethinking the combination of proton exchanger inhibitors in cancer therapy. Metabolites. 2018;8(1).

Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, et al. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs. J Natl Cancer Inst. 2004;96(22):1702-13.

Ergül M, Ergül M. Protein pump inhibitors esomeprazole and pantoprazole increase the chemosensitivity of Cml cells against imatinib. Cumhuriyet Med J. 2018 Dec 1;40(4):351-5.

Marino ML, Fais S, Djavaheri-Mergny M, Villa A, Meschini S, Lozupone F, et al. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells. Cell Death Dis. Nature Publishing Group. 2010;1(10):1-9.

Patlolla JMR, Zhang Y, Li Q, Steele VE, Rao CV. Anti-carcinogenic properties of omeprazole against human colon cancer cells and azoxymethane-induced colonic aberrant crypt foci formation in rats. Int J Oncol. 2012;40(1):170-5.

Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, et al. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells. PLoS One. 2011;6(5).

Song T, Jeon HK, Hong JE, Choi JJ, Kim TJ, Choi CH, et al. Proton pump inhibition enhances the cytotoxicity of paclitaxel in cervical cancer. Cancer Res Treat. 2017;49(3):595-606.

Lindner K, Borchardt C, Schöpp M, Bürgers A, Stock C, Hussey DJ, et al. Proton pump inhibitors (PPIs) impact on tumor cell survival, metastatic potential and chemotherapy resistance, and affect the expression of resistance-relevant miRNAs in esophageal cancer. J Exp Clin Cancer Res. 2014;33(1):1-12.

Wang X, Liu C, Wang J, Fan Y, Wang Z. Proton pump inhibitors increase the chemosensitivity of patients with advanced colorectal cancer Oncotarget. 2017;8(35):58801-8.